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Total Synthesis of 34‐Hydroxyasimicin and Its Photoactive Derivative for Affinity Labeling of the Mitochondrial Complex I
Author(s) -
Han Hongna,
Sinha Mantosh K.,
D'Souza Lawrence J.,
Keinan Ehud,
Sinha Subhash C.
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305557
Subject(s) - chemistry , stereochemistry , acetogenin , dihydroxylation , derivative (finance) , sharpless asymmetric dihydroxylation , photoaffinity labeling , total synthesis , wittig reaction , enantioselective synthesis , coupling reaction , combinatorial chemistry , binding site , biochemistry , catalysis , medicine , annonaceae , financial economics , economics , traditional medicine
The asymmetric total synthesis of the 34‐hydroxyasimicin and its 3‐(4‐benzoylphenyl)propionate ester was achieved by means of a convergent synthetic strategy. This ester, which contains eight asymmetric centers, represents the first photoaffinity‐labeling agent that is derived from an Annonaceous acetogenin. The key transformations in the synthesis include the Sharpless asymmetric dihydroxylation reaction, the Wittig olefination reaction, an oxidative cyclization reaction with rhenium (vii) oxide, the Williamson etherification reaction, and a palladium‐catalyzed cross‐coupling reaction. Use of the target molecule for photoaffinity‐labeling studies of bovine mitochondrial NADH‐ubiquinone oxidoreductase (Complex I) may shed light on the structure/function of this intricate enzyme and on the origin of the high antitumor activity exhibited by the Annonaceous acetogenins.